title: An extended database of keratin binding.
abstract: Diffusion modeling of dermal absorption relies in large part on high quality input data. Currently, estimates of corneocyte-phase partitioning are based on an analysis of a dataset of limited size and diversity. Therefore, we have updated and broadened the analysis. For this purpose, binding coefficients to different keratins, namely, bovine hoof and horn, human delipidized callus, human delipidized stratum corneum (SC), human nail, human hair, and sheep wool were collected from the literature. In addition, binding coefficients to hoof/horn and delipidized SC were measured for eight hydrophilic compounds including three ionizable compounds that were measured at different pH values. Important results are: (i) only hoof/horn, callus, and delipidized SC are suitable keratins for estimating corneocyte protein binding; (ii) binding coefficients to hoof/horn, callus, and delipidized SC can be predicted from the octanol-water partition coefficients log K(o/w) confirming the analysis of the limited dataset; (iii) binding of ionizable compounds can be predicted by correcting log K(o/w) for pH; (iv) the correlation derived for the extended database is steeper than the relationship derived for the limited dataset. This has consequences for the estimates of SC partition and diffusion coefficients for diffusion modeling of dermal absorption. .
authors.affiliation: Saarland University, Biopharmaceutics and Pharmaceutical Technology, Saarbruecken, Germany. st.hansen@mx.uni-saarland.de
authors.forename: Steffi
authors.initials: S
authors.lastname: Hansen
authors.forename: Dominik
authors.initials: D
authors.lastname: Selzer
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Schaefer
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
mesh_terms: D000818:Animals; D002417:Cattle; D016208:Databases, Factual; D006801:Humans; D007633:Keratins / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012756:Sheep; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D007633:Keratins